Pediatrics and Neonatology (2012) 53, 171e177

Available online at www.sciencedirect.com

journal homepage: http://www.pediatr-neonatol.com

ORIGINAL ARTICLE

Prevalence and Morbidity of Late Preterm Infants: Current Status in a Medical Center of Northern Taiwan
Ming-Luen Tsai, Reyin Lien*, Ming-Chou Chiang, Jen-Fu Hsu, Ren-Huei Fu, Shih-Ming Chu, Chang-Yo Yang, Peng-Hong Yang
Division of Neonatology, Department of Pediatrics, Chang Gung Childrens Hospital, Chang Gung University, College of Medicine, Taoyuan, Taiwan Received May 27, 2011; received in revised form Jul 7, 2011; accepted Jul 14, 2011

Key Words
late preterm; morbidity; near-term; readmission

Background: Late preterm denes infants born at 340/7 through 366/7 weeks gestation, which comprise a majority of preterm births. These infants were treated clinically as nearterm in the past, but recent studies have implied increased morbidities that differentiate late preterm and term infants. The purpose of this study was to examine the prevalence and clinical complications that could be associated with late preterm birth, as compared to term. Methods: This was a retrospective cohort study that reviewed infants born in a medical center in Northern Taiwan during a 2-year period between 2008 and 2009. Maternal obstetrical factors, neonatal demographic distributions, and neonatal complications were compared between full-term and late preterm deliveries. Results: During the study period, there were 7998 live births in the institute, including 6507 term and 1491 preterm infants. Of the latter, there were 914 (61.3 %) born after 34 weeks gestation. The Neonatal Intensive Care Unit (NICU) (including a special care nursery) admission rate was higher in late preterm infants when compared to term (36% vs. 2%), and was 74%, 43%, and 21% in infants born at 34, 35, and 36 weeks gestation, respectively. Compared with term infants, late-preterm infants had longer hospital stay if admitted to NICU (including special care nursery) (17 days vs. 10 days), and they were associated with increased risk of neonatal morbidities, including respiratory distress syndrome (2.6% vs. 0.02%), respiratory distress of other etiologies (16% vs. 2%), culture-proven sepsis (0.7% vs. 0.2%), hypoglycemia (3% vs. 0.4%), temperature instability (0.4% vs. 0.05%), feeding difculty (2% vs. 0.4%), and hyperbilirubinemia needing phototherapy (14% vs. 3%). Late-preterm infants also had higher hospital readmission rate (4.4 % vs. 2.3%, p < 0.001) and neonatal mortality rate (0.3% vs. 0.08%, p Z 0.03).

* Corresponding author. Division of Neonatology, Department of Pediatrics, Chang Gung Childrens Hospital, Number 5, Fu-Shing Street, Kweishan, Taoyuan 33305, Taiwan. E-mail address: reyinl@adm.cgmh.org.tw (R. Lien). 1875-9572/$36 Copyright 2012, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. All rights reserved. doi:10.1016/j.pedneo.2012.04.003

172

M.-L. Tsai et al
Conclusion: Late-preterm infants have increased risk of neonatal morbidities associated with organ immaturity. The results of this study emphasize the importance of judicious obstetrical decision-making when considering late preterm delivery, and the need to set up anticipatory clinical guidelines for the care of late preterm infants. Copyright 2012, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. All rights reserved.

1. Introduction
Preterm birth, dened as birth that occurs on or before the end of the 37th week (259th day) of pregnancy, counting from the rst day of the last menstrual period, is a conventional medical terminology endorsed by the American Academy of Pediatrics (AAP), the American College of Obstetricians and Gynecologists (ACOG), and the World Health Organization.1,2 Although preterm infants is a category known for its high mortality and various morbidities, the overall incidence of prematurity-related complications decreases signicantly if the infant was born after 34 weeks gestational age. In obstetric and pediatric practice, those infants born with less degree of prematurity are often considered functionally as full-term, and often are cared for in the well-baby nursery after birth. It was not until the last decade that special health concerns of these near-term infants arose.3,4 Mounting reports identied increased morbidities that differentiate late preterm and term infants. Furthermore, there was an awakening concern about using the term "near-term," which connotes that the infant is almost term and almost fully mature, might lead health care professionals to underestimate the inherent risks to these infants. General consensus came with the 2005 workshop, Optimizing Care and Outcome of the Near-Term Pregnancy and the Near-Term Newborn Infant, sponsored by the National Institutes of Health, which recommended that infants born at 340/7 through 366/7 weeks gestation after the onset of the mothers last menstrual period be referred to as late preterm to emphasize that these infants are preterm and, as such, are at risk of immaturity-related medical complications.5 In past decades, rising trend of preterm births was caused by an increase in the birth rate of late preterm infants.6 In those infants born late preterm, increased morbidities related to physiologic immaturity of the respiratory, metabolic, neurologic, and immunologic systems have been observed.7 It was also noted that they had a higher rate of hospital readmission during the neonatal period.8 It is important to discern the epidemiology and the actual neonatal morbidities of late preterm delivery, so that evidence can be provided to guide obstetrical decision-making and to direct anticipatory care for infants at risk. To our knowledge, there has been no previous study reported from Taiwan. The aim of our study was to examine the prevalence and clinical complications that could be associated with late preterm birth, as compared to term.

2. Methods
This was a retrospective cohort study of all late preterm live births (340/7 to 366/7 weeks of gestation) during the

2-year period between January 2008 and December 2009 in Chang Gung Medical Center, Lin Kou, Taiwan. Patients were identied, and the relevant clinical information was collected from electronic medical records. Full-term infants (370/7 to 406/7 weeks of gestation) born in the same institute during the same period were chosen and served as control group. In those infants who were admitted to special care units other than well baby nursery, their maternal obstetrical factors and neonatal demographic distributions were collected. Maternal obstetrical factors included hypertensive disorder of pregnancy (chronic hypertension, pregnancy-induced hypertension, and preeclampsia), diabetes (gestational and established), mode of delivery (cesarean section or vaginal delivery), indication for delivery (onset of labor, rupture of amniotic membrane, antepartum hemorrhage, abruption placentae, or fetal distress), indication for cesarean section (previous cesarean section, placenta previa, breech presentation, or unclear), multiple pregnancies (twins or triplets), and pregnancy outcome of major neonatal congenital anomalies such as pulmonary hypoplasia, congenial heart disease, structural malformation, and chromosomal anomalies. Demographic features of the newborn included gestational age (calculated from onset of the mothers last menstrual period), sex, birth weight (in grams obtained after delivery within 1 hour after birth), and Apgar scores at 1 and 5 minutes after birth. Outcome measures of neonatal complications included neonatal morbidities, admission to the neonatal intensive care unit (NICU; including special care nursery), duration of hospital stay if admitted to NICU or special care nursery, rate of hospital readmission within the neonatal period, and neonatal death. Criteria of NICU or special care nursery admission could be any of the following: birth body weight less than 2200 g, gestational age less than 34 weeks, respiratory or circulatory instability, hypoglycemia, signicant hyperbilirubinemia, suspected sepsis, or the need for close monitoring as assessed by a neonatologist. Neonatal morbidities included respiratory complications [respiratory distress syndrome (RDS), transient tachypnea of newborn (TTN), persistent pulmonary hypertension (PPHN), pneumonia and air leak syndrome], apnea events (cessation of breathing for longer than 20 seconds, or any duration if accompanied by cyanosis and bradycardia), culture-proven sepsis (early-onset or late-onset, divided as infections occurring before and after 1 week of life), neurologic complications (convulsion, periventricular leukomalacia, intraventricular or intracranial hemorrhage), hypoglycemia (blood glucose level of less than 40 mg/dL in capillary or venous blood sample, and criteria for checking serum glucose: small for gestational age, infants of diabetes mothers, giant babies with birth weight more than 4000 g, or clinical symptoms associated with

Morbidity of late preterm infants hypoglycemia), temperature instability (core body temperature of less than 36.0 C or higher than 38.0 C, detected within 4 hours after birth and every 8 hours until discharge), hyperbilirubinemia needing phototherapy (indication for phototherapy based on guidelines from AAP 20049), hypocalcemia, anemia needing blood transfusion, and feeding difculty. Diagnosis of congenital heart disease was made by pediatric cardiologist with conrmation using coloredDoppler echocardiography. Symptomatic patent ductus arteriosus (PDA) was diagnosed according to cardiovascular dysfunction score,10 clinical signs of congestive heart failure and high ratio of left atrium to aortic root size. Treatment of symptomatic PDA could be medical or by surgical ligation. Statistical analysis was performed using SPSS software version 12.0 (SPSS by IBM, version 12.0). Data analysis was performed with the Pearson chi-square test for categorical variables. Continuous variables were analyzed using the independent t-test for between-group comparison. Differences were considered statistically signicant when p < 0.05.

173 2290 530 g in late preterm and 3090 530 g in full-term infants. There were no signicant differences of gender distribution or Apgar scores at 1 minutes and 5 minutes between those two groups. The maternal obstetrical characteristics in the subset of those infants who were admitted to NICU or special care nursery are summarized in Table 2. In these infants, the most frequent indication for delivery was onset of labor pain, in both late preterm and term infants. However, only 29.1% of the late preterm infants and 62.2% of the term infants were delivered because of onset of labor in this specic subset of newborns. The second most common indication for delivery was rupture of membranes, in 28.8% of late preterm and 19.8% of term infants (p Z 0.002). The other indication for delivery included ante-partum hemorrhage or abruptio placentae (7.6% vs. 1.3%, late preterm and term, p < 0.001), fetal distress (11.1% vs. 5.4%, p < 0.001). In this subset of newborns, late preterm infants were more likely to be delivered by Cesarean section than term infants (76.1% vs. 36.2%, p < 0.001). Although the indication for Cesarean section might have been multiple (e.g., antepartum hemorrhage and fetal distress), those documented in the medical records in order of decreasing frequency were breech presentation, previous C-section, fetal distress, and antepartum hemorrhage in late preterm infants, and previous C-section, breech presentation, fetal distress and antepartum hemorrhage in term infants. Also, as commonly seen in obstetrical practice, those with multiple gestations tend to deliver before term. Sixty-three (84%) of the 75 sets of twins and all three sets (100%) of triplets were born before completion of 37 weeks of gestation. It was also shown in our study that mothers with complicated pregnancies, e.g., hypertensive disorder of pregnancy and diabetes, tend to deliver before term. Table 3 depicts neonatal morbidities of late preterm and term infants. The mean length of the hospital stay in the NICU or special care nursery for all late preterm infants was 17 days compared with 10 days for term infants (p < 0.001). Late preterm infants had signicantly higher risk of developing respiratory complications than did the term infants: RDS (2.6% vs. 0.02%), TTN (12.8% vs. 1%), PPHN (0.4% vs. 0.03%), and pneumonia (2.8% vs. 0.6%). Apnea events only occurred in late preterm infants (2.1% vs. 0%, p < 0.001). There was no difference in the occurrence of air-leak syndrome between these two groups (0.3% vs. 0.1 %, p Z 0.145). Late preterm infants were more prone to have cultureproven sepsis than term infants (0.7% vs. 0.2%, p Z 0.02), but the difference was only seen in late-onset (0.5% vs. 0.1%, p Z 0.004) and not early-onset sepsis. In the earlyonset sepsis, there was one infant born at 34 weeks gestation who developed group B streptococcus infection

3. Results
During the study period, there were 7998 live births in the institute, including 6507 term and 1491 preterm infants. Of the latter, there were 914 (61.3%) infants born after 34 weeks gestation. Overall, these late preterm infants had high neonatal mortality rate of 0.3%, as compared with 0.08% in term infants (p Z 0.03). There were 36.8% of the late preterm infants and 7.2% of the full-term infants admitted to NICU (including special care nursery). These data are shown in Table 1. Three patients in the late preterm group died, each due to hydrops fetalis, severe respiratory distress syndrome and congenital myopathy, respectively. On the other hand, ve term infants died, two of perinatal asphyxia, two of severe respiratory distress, and one of Ebstein anomaly. The NICU admission rate was higher in late preterm infants when compared to term infants (36.8% vs. 7.2%, p < 0.001), and was 73.7%, 43.4%, and 20.9% in infants born at 34, 35, and 36 weeks gestational age, respectively. Late preterm infants also had higher rate of hospital readmission during neonatal period when compared to full-term infants (4.4 % vs. 2.3%, p < 0.001). Reasons for readmission (data not shown) in order of decreasing frequency were hyperbilirubinemia needed phototherapy, urinary tract infection, lower respiratory tract infection and feeding-related problems in both late preterm and full-term infants. Birth weight (mean SD) of NICU or special care nursery admission infants was

Table 1

Incidence of NICU/special care nursery admission/readmission and mortality rate in late preterm and term infants. Late preterm 34 wks (n Z 157) 35 wks (n Z 274) 119 (43.4) 13 (4.7) 1 (0.4) 36 wks (n Z 483) 101 (20.9) 17 (3.5) 1 (0.2) Total (n Z 914) 336 (36.8) 40 (4.4) 3 (0.3) 471 (7.24) 150 (2.3) 5 (0.08) < 0.001 < 0.001 0.03 Term (n Z 6507) p value*

Admission (n, %) Readmission (n, %) Mortality (n, %)

116 (73.9) 10 (6.4) 1 (0.6)

*Total late preterm infants compared with term infants.

174
Table 2 Maternal obstetrical factors of NICU/special care nursery admitted infants. Late preterm 34 wks (n Z 123) Indication for delivery Onset of labor (n, %) Rupture of amniotic membrane (n, %) Antepartum hemorrhage/ abruption placentae (n, %) Fetal distress (n, %) Mode of delivery Cesarean section (n, %) Vaginal delivery (n, %) Indication for C-section Breech presentation (n, %) Previous cesarean section (n, %) Placenta previa (n, %) Elective C-section (n, %) Multiple gestations (n) Twins (n) Triplets (n) Other complications of pregnancy Diabetes (n, %)y HDP (n, %)z Major congenital anomalies of newborn (n, %) 37 (30.1) 41 (33.3) 11 (8.9) 12 (9.8) 95 (77.2) 28 (22.8) 40 (32.5) 17 (13.8) 6 (4.9) 1 (0.8) 22 20 2 35 wks (n Z 130) 37 (28.5) 40 (30.8) 11 (8.5) 23 (17.7) 93 (71.5) 37 (28.5) 33 (25.4) 16 (12.3) 10 (7.7) 3 (2.3) 23 23 0 36 wks (n Z 115) 33 (28.7) 25 (21.7) 6 (5.2) 6 (5.2) 92 (80) 23 (20) 29 (25.2) 21 (18.3) 10 (8.7) 4 (3.5) 21 20 1 Total (n Z 368) 107 (29.1) 106 (28.8) 28 (7.6) 41 (11.1) 280 (76.1) 88 (23.9) 102 (27.7) 54 (14.7) 26 (7.1) 8 (2.2) 66 63 3 Term (n Z 611)

M.-L. Tsai et al

p value*

380 (62.2) 121 (19.8) 8 (1.3) 33 (5.4) 221 (36.2) 390 (63.8) 39 (6.4) 51 (8.3) 8 (1.3) 53 (8.7) 12 12 0

< 0.001 0.002 < 0.001 < 0.001 < 0.001

< 0.001 0.002 < 0.001 < 0.001 < 0.001 < 0.001

6 (4.9) 18 (14.6) 7 (5.7)

6 (4.6) 19 (14.6) 8 (6.2)

7 (6.1) 15 (13) 11 (9.6)

19 (5.2) 52 (14.1) 26 (7.1)

15 (2.5) 25 (4.1) 34 (5.6)

< 0.025 < 0.001 0.343

*Total late preterm infants compared with term infants. HDP Z hypertensive disorder of pregnancy; NICU Z neonatal intensive care unit. y Including gestational and established. z Hypertensive disorder of pregnancy including chronic hypertension, pregnancy-induced hypertension, and preeclampsia.

and two full-term infants, one with group B streptococcus and one with Escherichia coli infection, respectively. Other morbidities that occurred more often in late preterm than term infants included convulsion (0.8% vs. 0.1 %, p < 0.001), periventricular leukomalacia (PVL; 0.2% vs. 0.02%, p Z 0.04), feeding-related problems (2.2% vs. 0.4%, p < 0.001), hyperbilirubinemia that required phototherapy (14.4% vs. 3.2%, p < 0.001), and anemia requiring blood transfusion (3.5% vs. 0.3%, p < 0.001). Metabolically, hypoglycemia (3% vs. 0.4%, p < 0.001), temperature instability (0.44% vs. 0.05%, p < 0.001), and hypocalcemia (4.4% vs. 0.2%, p < 0.001) all occurred more often among late preterm infants than term infants. The late preterm infants not only were more likely to have PDA diagnosed after 72 hours of life (2.4% vs. 0.3%, p < 0.001), their PDA were also more likely to cause a hemodynamically aberration and needed medical and/or surgical intervention (Table 4). Six of the 22 late preterm infants who had PDA needed medical (three newborns) and/or surgical (three newborns) intervention to alleviate their symptoms caused by PDA.

4. Discussion
This study showed that in our hospital, a medical center of northern Taiwan with a level III NICU and around 4000

annual deliveries, 18.6% of the inborn infants were born preterm, and 61.3% of the preterm infants were born between 340/7 and 366/7 weeks gestation. Thus, of all the newborn infants delivered, more than one out of every ten (11.4%) was born late preterm. Our results showed that late preterm infants not only had a higher neonatal mortality rate, they also had ve times the risk of being admitted to NICU or special care nursery, and they were more likely to have hospital readmission during neonatal period, as compared to term infants. From our study, we also found that both neonatal mortality and the risk of NICU or special care nursery admission proved to increase for every week of decrease in gestational age, as they were 0.2%, 0.4%, and 0.6% for perinatal mortality and 21%, 43%, and 74% for NICU or special care nursery admission if born at 36, 35, and 34 weeks gestation, respectively. Similar results were reported by Young and coauthors,11 as the neonatal mortality of late preterm infants in Utah being 0.38%, 0.5% and 0.8%, and by Esobar and others,8 of 25%, 54%, and 88% of NICU admission rate if born at 36, 35, and 34 weeks gestational age. A large population-based cohort study from the United States and Canada showed that preterm infants are at high relative risks for infant death.3 In our study, we discovered a hospital readmission rate of 3.5% in our late preterm infants, as compared to 4.8% reported in the literature.12 Although late preterm infants were more likely both to be admitted to NICU or

Morbidity of late preterm infants

Table 3 Neonatal complications of late preterm and term infants. Late preterm 34 wks (n Z 157) NICU hospital stay (mean SD), d Respiratory morbidity RDS (n, %) TTN (n, %) PPHN (n, %) Air-leak syndrome (n, %) Pneumonia (n, %) Apnea events (n, %) Culture-proven sepsis (n, %) Early onset (n, %) Late onset (n, %) Neurologic morbidity Convulsions (n, %) PVL (n, %) IVH (n, %) Metabolic morbidity Hyperbilirubinemia needing phototherapy (n, %) Hypoglycemia (n, %) Temperature instability (n, %) Hypocalcemia (n, %) Feeding difculty (n, %) Anemia needing blood transfusion (n, %) 19 10 10 (6.3) 52 (33.1) 1 (0.6) 1 (0.6) 10 (6.4) 10 (6.4) 1 (0.6) 1 (0.6) 0 1 (0.6) 1 (0.6) 1 (0.6) 53 (33.7) 11 (7.0) 1 (0.6) 18 (11.5) 4 (2.5) 13 (8.2) 35 wks (n Z 274) 18 14 8 (2.9) 36 (13.1) 0 (0) 0 (9) 8 (2.9) 6 (2.2) 4 (1.5) 0 4 (1.5) 2 (0.7) 0 (0) 0 (0) 42 (16.8) 9 (3.3) 2 (0.7) 12 (4.4) 8 (2.9) 11 (4) 36 wks (n Z 483) 15 12 6 (1.2) 29 (6) 3 (0.6) 2 (0.4) 8 (1.6) 3 (0.6) 1 (0.2) 0 1 (0.2) 5 (1.0) 1 (0.2) 0 (0) 1 (6.8) 9 (1.9) 1 (0.2) 10 (2.1) 8 (1.6) 8 (1.7) Total (n Z 914) 17 12 24 (2.6) 117 (12.8) 4 (0.4) 3 (0.3) 26 (2.8) 19 (2.1) 6 (0.7) 1 (0.1) 5 (0.5) 8 (0.8) 2 (0.2) 1 (0.1) 132 (14.4) 29 (3) 4 (0.44) 40 (4.4) 20 (2.2) 32 (3.5) Term (n Z 6507) 10 10 1 (0.02) 67 (1) 2 (0.03) 8 (0.1) 44 (0.6) 0 (0) 10 (0.2) 2 (0.03) 8 (0.1) 10 (0.1) 1 (0.02) 0 (0) 209 (3.2) 25 (0.4) 3 (0.05) 12 (0.2) 25 (0.4) 21 (0.3)

175

p value*

< 0.001 < 0.001 < 0.001 0.003 0.145 < 0.001 < 0.001 0.002 0.268 0.004 < 0.001 0.042 0.123 < 0.001 < < < < < 0.001 0.001 0.001 0.001 0.001

*Total late preterm infants compared with term infants. IVH Z intraventricular hemorrhage; NICU Z neonatal intensive care unit; PPHN Z persistent pulmonary hypertension; PVL Z periventricular leukomalacia; RDS Z respiratory distress syndrome; SD Z standard deviation; TTN Z transient tachypnea of newborn.

special care nursery and to have hospital readmission, the hospital readmission rate of those discharged from NICU or special care nursery was not different between late preterm and term infants in our study (2.3% and 2.1%, respectively). Late preterm infants in our study were found to have more neonatal complications compared to full-term infants. Nearly 19% of late preterm infants in our study had clinical symptoms of respiratory distress, and the etiologies included RDS, TTN, PPHN, pneumonia, and airleak syndrome. Understandably, all the above etiologies other than air-leak syndrome were seen more often in late preterm than in term infants. Birth in the absence of labor

and hence lack of clearance of lung uid, or relative deciency of pulmonary surfactant due to immaturity could all be key factors for respiratory distress of late preterm infants.13 In this study, we noted that 2.2% of the late preterm infants experienced apnea events, and the risk of apnea does increase with decrease of every week in gestational age from 36e34 weeks. No term infants experienced apnea events in our study. Extremely premature infants are considered immunedecient and have a signicantly higher risk of infection than term newborns. However, the ontogeny and sequences of maturation of the immune system during late preterm gestation has not been well studied and remains unclear.14

Table 4

Cardiovascular system of late preterm infants and term infants. Late preterm infants 34 wk (n Z 157) 35 wk (n Z 274) 8 (2.9) 3 (1.1) 0 (0) 36 wk (n Z 483) 9 (1.9) 2 (0.4) 2 (0.4) Total (n Z 914) 22 (2.4) 6 (0.7) 4 (0.4) 22 (0.3) 2 (0.03) 5 (0.07) < 0.001 < 0.001 0.003 Term (n Z 6507) p value*

PDA (n, %) PDA needing intervention (n, %) Complex CHD (n, %)

5 (3.2) 1 (0.6) 2 (1.2)

*Total late preterm infants compared with term infants. CHD Z congenital heart disease; PDA Z patent ductus arteriosus.

176 We found that late preterm infants had three times higher risk of culture-proven sepsis as compared to full-term infants, but the difference was seen in late-onset sepsis only. This could very well have resulted from longer hospital stay of late preterm infants and lead us to the assumption that beyond 34 weeks gestation, passage of maternal immunoglobulin and the fundamental immunity is likely to be completed. High risks of variable metabolic aberrations in late preterm infants make them physiologically unt to leave the maternal utero-placental unit. Mechanisms to cause such metabolic symptoms are often interrelated. For example, late preterm infants suffered from temperature instability because of relatively immature epidermal barrier, a higher body surface area to weight ratio, and increased heat loss from frequent delivery room interventions.15 In turn, hypothermia, along with immature hepatic glycogenolysis, limited enteral intake due to gastrointestinal immaturity, and poor suction-swallow coordination can lead to hypoglycemia. In our study, late preterm infants had signicantly higher risks of temperature instability, hypoglycemia, hypocalcemia, and hyperbilirubinemia needing phototherapy than term infants. Hyperbilirubinemia was reported as the major reason for hospital readmission in late preterm infants.8,16 There was also a remarkable risk of neonatal neurologic disorders noted in our late preterm infants, specically seizure and periventricular leukomalacia. This puts the late preterm infants at risk for impaired long-term neurodevelopmental outcome. In fact, cerebral palsy, developmental delay, and mental retardation in early childhood and unfavorable early-school age performance in late preterm infants have been reported.17,18 Physiologic closure of the ductus arteriosus relies on a postnatal increase in arterial oxygen tension and a decline in pulmonary vascular resistance. In our study, late preterm infants were more likely to have PDA diagnosed after 72 hours of life, and hemodynamically significant PDA that required intervention. In normal full-term neonates, constriction of the ductus usually results in functional hemodynamic closure soon after birth19; by contrast, closure is delayed in premature babies, because of the thinner muscular media of the ductus and continued response to prostaglandin E2 and nitric oxide.20,21 What we observed of PDA in late preterm infants might represent the vascular immaturity in this population, or it could have arisen from perpetuation of hypoxia secondary to pulmonary disorders that late preterm infants also suffered from. This study is limited due to its retrospective nature. One major defect in such study design could be that all information was based on medical records of this medical center. If any infants born in this hospital later on were admitted to our hospitals for medical care within 1 month of age, discrepancies in the results of this study could have been caused due to selective bias. The rates of morbidity and mortality would be underestimated within both groups due to lack of complete follow-up. And because of such pitfall in study design, we were only able to examine relevant obstetrical details in the cohort of mothers whose infant were admitted to NICU or special care nursery.

M.-L. Tsai et al In this cohort of patients, the most common reasons for delivery of an infant late preterm was onset of labor and rupture of amniotic membranes. There was no data to support that interventions to delay delivery of the late preterm fetus would lessen these morbidities.22,23 Although as of the latest ACOG guideline, delivery is recommended when premature rupture of amniotic membrane (PROM) occurs at or beyond 34 weeks of gestation,24 there have been increasing controversies in aggressive versus conservative obstetrical management in PROM during late preterm gestation.25 It is prudent that decision-making with the early delivery of late preterm infants should be weighed against the risk for neonatal and maternal morbidity, but substantial progress in the care of preterm infants as a whole in the past decades had possibly attributed to a more cavalier obstetrical approach in the situation of late preterm delivery. However, there has been accumulating evidence of detrimental neonatal or longterm outcome in late preterm infants. It is also clear that pregnancy complications themselves that result in late preterm delivery may by adversely affect neonatal outcome independently of late prematurity. However, due to our study design, we were not able to distinguish between the effects were from maternal obstetrical factor or dysmaturity of late preterm infant per se. Shapiro-Mendoza and colleagues26 reported that independent effect of late preterm birth on newborn morbidity was nearly sevenfold that of the independent effect of any of the selected maternal medical conditions, and that newborn morbidity increased greatly if combined with maternal medical conditions, especially antepartum hemorrhage and hypertensive disorders. On the other hand, a study by Melamed and coauthors27 revealed that low-risk, spontaneous, singleton, late preterm deliveries were still independently associated with an increased risk of neonatal morbidities. Our study is the rst to examine prevalence and morbidity of late preterm infants in Taiwan, and our ndings support the fact that consistent with whats observed in other developed countries, late preterm delivery has a signicant local prevalence, and it is associated with considerable neonatal complications. In conclusion, in this rst study focused on late preterm infants in Taiwan, we found high prevalence of late preterm deliveries, and that late preterm infants are at considerable risk for neonatal mortality and morbidities. The results of this study emphasize the importance of judicious obstetrical decision-making when considering late preterm delivery and the need to set up anticipatory clinical guidelines for the care of late preterm infants.

References
1. World Health Organization. Sexual and reproductive health. 2010. Available at: http://www.who.int/reproductivehealth/ en/ [Date accessed: July 7, 2011]. 2. American Academy of Pediatrics. American College of Obstetricians and Gynecologists. Guidelines for perinatal care. 5th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2005. 3. Kramer MS, Demissie K, Yang HM, et al. The contribution of mild and moderate preterm birth to infant mortality. JAMA 2000;284:843e9.

Morbidity of late preterm infants

4. Moutquin J- M. Classication and heterogeneity of preterm birth. BJOG 2003;110:30e3. 5. Raju TN, Higgins RD, Stark AR, et al. Optimizing care and outcome for late-preterm (near-term) infants: a summary of the workshop sponsored by the National Institute of Child Health and Human Development. Pediatrics 2006;118:1207e14. 6. Davidoff MJ, Dias T, Damus K, et al. Changes in the gestational age distribution among U.S. singleton births: impact on rates of late preterm birth, 1992 to 2002. Semin Perinatol 2006;30:8e15. 7. Picone S, Paolillo P. Neonatal outcomes in a population of late-preterm infants. J Matern Fetal Neonatal Med 2010; 23(S3):116e20. 8. Escobar GJ, Greene JD, Hulac P, et al. Rehospitalisation after birth hospitalisation: patterns among infants of all gestations. Arch Dis Child 2005;90:125e31. 9. Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004;114:297e316. 10. Yeh TF, Raval D, Luken J, Thalji A, Lilien L, Pildes RS. Clinical evaluation of premature infants with patent ductus arteriosus: a scoring system with echocardiogram, acid-base, and blood gas correlations. Crit Care Med 1981;9:655e7. 11. Young PC, Glasgow TS, Li X, et al. Mortality of late-preterm (near-term) newborns in Utah. Pediatrics 2007;119:e659e65. 12. Shapiro-Mendoza CK, Tomashek KM, Kotelchuck M, et al. Risk factors for neonatal morbidity and mortality among healthy, late preterm newborns. Semin Perinatol 2006;30:54e60. 13. Jain L, Eaton DC. Physiology of fetal lung uid clearance and the effect of labor. Semin Perinatol 2006;30:34e43. 14. Clapp DW. Developmental regulation of the immune system. Semin Perinatol 2006;30:69e72. 15. Laptook A, Jackson GL. Cold stress and hypoglycemia in the late preterm (near-term) infant: impact on nursery of admission. Semin Perinatol 2006;30:24e7. 16. Escobar GJ, Joffe S, Gardner MN, Armstrong MA, Folck BF, Carpenter DM. Rehospitalization in the rst two weeks after discharge from the neonatal intensive care unit. Pediatrics 1999;104:e2.

177
17. Morse SB, Zheng H, Tang Y, Roth J. Early school-age outcomes of late preterm infants. Pediatrics 2009;123:e622e9. 18. Petrini JR, Dias T, McCormick MC, Massolo ML, Green NS, Escobar GJ. Increased risk of adverse neurological development for late preterm infants. J Pediatr 2009;154:169e76. 19. Gentile R, Stevenson G, Dooley T, Franklin D, Kawabori I, Pearlman A. Pulsed Doppler echocardiographic determination of time of ductal closure in normal newborn infants. J Pediatr 1981;98:443e8. 20. Silver MM, Freedom RM, Silver MD, Olley PM. The morphology of the human newborn ductus arteriosus: a reappraisal of its structure and closure with special reference to prostaglandin E1 therapy. Hum Pathol 1981;12:1123e36. 21. Clyman RI, Waleh N, Black SM, Riemer RK, Mauray F, Chen Y- Q. Regulation of ductus arteriosus patency by nitric oxide in fetal lambs: the role of gestation, oxygen tension, and vasa vasorum. Pediatr Res 1998;43:633e44. 22. Mercer BM, Crocker LG, Boe NM, Sibai BM. Induction versus expectant management in premature rupture of the membranes with mature amniotic uid at 32 to 36 weeks: a randomized trial. Am J Obstet Gynecol 1993;169:775e82. 23. Naef RWIII, Allbert JR, Ross EL, Weber BM, Martin RW, Morrison JC. Premature rupture of membranes at 34 to 37 weeks gestation: aggressive versus conservative management. Am J Obstet Gynecol 1998;178:126e30. 24. ACOG Committee on Practice Bulletins - Obstetrics. ACOG Practice Bulletin No. 80: premature rupture of membranes. Clinical management guidelines for obstetrician-gynecologists. Obstet Gynecol 2007;109:1007e19. 25. Mateus J, Fox K, Jain S, Jain S, Latta R, Cohen J. Preterm premature rupture of membranes: clinical outcomes of latepreterminfants. Clin Pediatr (Phila) 2010;49:60e5. 26. Shapiro-Mendoza CK, Tomashek KM, Kotelchuck M, et al. Effect of late-preterm birth and maternal medical conditions on newborn morbidity risk. Pediatrics 2008;121:e223e32. 27. Melamed N, Klinger G, Tenenbaum-Gavish K, et al. Short-term neonatal outcome in low-risk, spontaneous, singleton, late preterm deliveries. Obstet Gynecol 2009;114:253e60.